Human milk (HM) has long been known to impart immunoprotection and to have growth-promoting qualities for the neonate that result in decreased morbidity and mortality. It is postulated that the live cells present in human milk (the macrophage being the predominant cell type after the third postnatal day) may be responsible, in part, for many of the bioactive properties of human milk. It is hypothesized that through the HMM's unique capability to survive in the newborn gut, the HMM provides both immunologic and maturational factors to the neonatal gut, particularly the proximal small intestine. By way of HMM's ability to migrate into submucosal layers of the gut, and be absorbed systemically as animal data suggest, the maternally derived mononuclear-phagocyte becomes a plausible mechanism of maternal-neonatal cell to cell communication. As such, it is further hypothesized that HMM and secreted TGFalpha isoforms with gut epithelial cells is presently unknown. In specific aim 1, both the qualitative and quantitative differences in serum TGF alpha isoforms of breast-fed vs. formula-fed infants will be measured by RIA and Western blot analysis to ascertain if exogenous TGFalpha derived from mother's milk is absorbed by the gut, affecting systemic TGFalpha isoform concentration and type. Specific aim 2 will measure the trophic effect of HMM and milk-derived TGFalpha isoforms vs. EGF on neonatal gut differentiation in separate in vitro monocyte and fetal small intestinal cell (FhS-74 and CCL-6) proliferation studies. The long term goal of this proposal is to develop a model of newborn gut maturation that takes into account the dynamic effect of mother's milk on her newborn.